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Effect of Depot Medoxyprogesterone Acetate on Immune Functions and Inflammatory Markers of HIV-Infected Women

Weinberg, Adriana MD*; Park, Jeong-Gun PhD; Bosch, Ronald PhD; Cho, Alice BSc*; Livingston, Elizabeth MD; Aweeka, Fran PharmD; Cramer, Yoninah MS; Watts, D. Heather MD; Luque, Amneris E. MD; Cohn, Susan E. MD, MPH#

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 February 2016 - Volume 71 - Issue 2 - p 137–145
doi: 10.1097/QAI.0000000000000850
Basic and Translational Science

Objectives: Depot medroxyprogesterone acetate (DMPA) was associated with increased HIV transmission and accelerated disease progression in untreated women. The potential underlying mechanisms include immune modulation. We evaluated the effect of a single DMPA injection on cell-mediated immunity (CMI), T-cell activation, T-cell regulation (Treg), and inflammation in HIV-infected women on combination antiretroviral regimen (cART).

Methods: Women with HIV plasma RNA 400 copies per milliliter on stable cART received DMPA and had immunologic and medroxyprogesterone acetate (MPA) measurements at baseline, 4 weeks [peak MPA concentration (Cmax)], and 12 weeks [highest MPA area under the concentration curve].

Results: At baseline, among 24 women with median age of 32 years and 622 CD4+ cells per microliter, ≥68% had HIV, varicella-zoster virus, phytohemagglutinin A and CD3/CD28 CMI measured by lymphocyte proliferation, and/or IFNγ/IL2 dual-color fluorospot. CMI did not significantly change after DMPA administration except for a 1.4-fold increase in IL2/IFNγ varicella-zoster virus fluorospot at week 12. T-cell activation decreased after DMPA administration, reaching statistical significance at week 12 for CD4+CD25+%. Treg behaved heterogeneously with an increase in CD8+FOXP3+% at week 4 and a decrease in CD4+IL35+% at week 12. There was a decrease in TGFβ at week 12 and no other changes in plasma biomarkers. Correlation analyses showed that high MPA Cmax and/or area under the concentration curve were significantly associated with increases of IFNγ HIV enzyme-linked ImmunoSpot, CD4+IL35+%, and CD4+TGFβ+% Treg and decreases of plasma IL10 from baseline to weeks 4 and/or 12.

Conclusions: A single dose of DMPA did not have immune-suppressive or pro-inflammatory effects in HIV-infected women on cART. Additional studies need to assess the effect of multiple doses.

*Department of Pediatrics, University of Colorado Denver Anschutz Medical Center, Aurora, CO;

Department of Biostatistics, Statistical and Data Analysis Center, Harvard School of Public Health, Boston, MA;

Department of Obstetrics/Gynecology/Maternal-Fetal Medicine, Duke University Medical Center, Durham, NC;

§Department of Clinical Pharmacology, University of California, San Francisco, CA;

Office of the Global AIDS Coordinator and Health Diplomacy, U.S. Department of State, Washington, DC;

Department of Infectious Diseases, University of Rochester School of Medicine and Dentistry, Rochester, NY; and

#Department of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL.

Correspondence to: Adriana Weinberg, MD.

The laboratory work reported in this publication was supported by N01HD33162 (97-07) to A.W.; the clinical work by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Numbers UM1 AI068634, UM1 AI068636, and UM1 AI106701; grant 1U01AI069511 and CRC grant UL-1RR02460 to the University of Rochester; 1U01AI069471 and CRC grant UL-1TR000150 to the Northwestern University; 1U01AI069513 to Cincinnati CRS; 1U01AI069481 to the University of Washington; UM1 AI069423-08, CTSA grant 1UL-1TR001111, CFAR grant P30 AI50410 to UNC Global CTU: Chapel Hill CRS and by UCSL PSL is under National Institutes of Health (NIH) grant 1U01AI068636. Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases of the NIH under award numbers UM1 AI068632 (IMPAACT LOC), UM1 AI068616 (IMPAACT SDMC), and UM1 AI106716 (IMPAACT LC), with cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health; and the statistical work by the National Institute of Allergy and Infectious Diseases cooperative agreement UM1 AI068634 to the Statistical and Data Analysis Center at the Harvard School of Public Health.

The authors have no conflicts of interest to disclose.

A.E.L. and S.E.C. equally contributed to this work.

Received May 15, 2015

Accepted August 31, 2015

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